The synthesis of 2,2-diethoxytetrahydrofuran (DETHF) described in the literature (Meerwein et al., Chem. Ber., 1956, 89:2060) is the reaction of .gamma.-butyrolactone with triethyloxonium tetrafluoroborate and the subsequent reaction of the resulting O-ethyllactonium tetrafluoroborate with sodium ethoxide. This synthesis produces ethyl ether as a byproduct; additionally, ethyl ether is required as a starting material in the manufacture of the triethyloxonium tetrafluoroborate. Thus, the process is not suitable for large-scale production because it involves substantial quantities of ethyl ether, which is low-boiling and inflammable. Furthermore, the process is unsuitable because of the presence of unstable, hygroscopic intermediates and because of the many time consuming operations required to be carried out in the process, such as isolation of the various intermediates.
An alternative method for preparing cyclic ortho esters derived from related lactones has been discussed by several researchers. See, Mir-Mohamad-Sadeghy et al., J. Org. Chem., 1983, 48:2237; Cornejo et al., J. Org. Chem., 1983, 48:3869; Pollart et al., J. Org. Chem., 1986, 51:3155. Following this method, a lactone is reacted with a dialkoxymethylium tetrafluoroborate to give the O-alkyllactonium tetrafluoroborate intermediate, which is then reacted with sodium ethoxide as in Meerwein (supra). However, the same drawbacks attend this procedure, namely: dialkoxymethylium tetrafluoroborate is prepared using boron trifluoride etherate as a starting material as well as ether and methylene chloride as solvents (Borch, J. Org. Chem., 1969, 34:627), other solvents such as methylene chloride and carbon tetrachloride are used throughout the process, and at each step intermediates are isolated prior to the next synthetic step.
It is therefore desirable to find an alternative method of synthesizing 2,2-dialkoxy cyclic ortho esters derived from lactones, such as 2,2-diethoxytetrahydrofuran, without the use of solvents, and in particular of ether. It is also desirable to find a synthetic process which avoids isolation of intermediates.